title: A unique case of de novo 5q33.3-q34 triplication with uniparental isodisomy of 5q34-qter.
abstract: De novo triplication together with uniparental disomy (UPD) is a rare genomic rearrangement, and, to our knowledge, co-occurrence has previously only been reported in two individuals. We encountered a patient with a suspected karyotype of 46,XX,del(5)(q33.1q33.3),dup(5)(q31.3q33.3) or (q33.1q35.1). Genetic analysis revealed tetrasomy of 5q33.3-q34 caused by de novo middle inverted triplication and uniparental isodisomy of 5q34-qter. Most clinical features in the patient were observed in previously reported cases of duplication overlapping with 5q33.3-q34, with the exception of hearing loss. The FOXI1 gene, which causes autosomal recessive deafness (OMIM 600791, DFNB4) when mutated, was contained within the uniparental isodisomy region (5q34-qter). However, no mutations were identified following Sanger sequencing of FOXI1. This is the first report of a patient with de novo triplication together with uniparental isodisomy of chromosome 5q. As segmental isodisomy is a post-fertilization error, it is thought to have occurred during mitosis just after fertilization via a U-type exchange, while inverted duplication could have occurred during meiosis or mitosis. This study reaffirms that the single nucleotide polymorphism (SNP) array is a powerful tool to screen for UPD in a single experiment, especially in cases of isodisomy.
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fujita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzumura
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Nakashima
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tsurusaki
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
authors.forename: Naoki
authors.initials: N
authors.lastname: Harada
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
mesh_terms: D000328:Adult; D058674:Chromosome Duplication; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D015894:Genome, Human; D005865:Gestational Age; D006801:Humans; D007621:Karyotyping; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy; D060888:Real-Time Polymerase Chain Reaction; D024182:Uniparental Disomy / Q000235:genetics*
keywords: 5q; SNP array; genomic rearrangement; triplication; uniparental isodisomy